Using isoelectric focusing (IEF) this laboratory has found oligoclonal IgG in 55% of synovial culture supernatants, and in 17% of RA sera or matched synovial fluid (Arth Rheum 27: 976,1984). In other studies this oligoclonal serum IgG and the RA synovial culture IgG with a common isoelectric point have been shown to share idiotypic (Id) cross-reactivity. Since anti-Id reagents provide one of the most powerful and specific ways of establishing the common identity of antibodies, and are often cross-reactive with antibodies of unrelated individuals directed against the same antigen, they will be used to predict the nature of the stimulating antigen(s) in RA. Anti-Id antibodies will be produced in mice (monoclonal), and in rabbits (polyclonal) against highly-purified, oligoclonal bands of RA synovial IgG. Monoclonal anti-Id will be bound to an immunoadsorbent to isolate larger amounts of cross-reacting IgG from the serum of the patient donating the synovium. This cross-reactive serum IgG will be used to screen viral, bacterial, and food antigens for reactivity which would link them to the pathogenesis of RA. Appropriately absorbed rabbit anti-Id will be used to screen the IgG of other RA synovial cultures or sera for cross-reactive idiotypic determinants which, if present, would suggest a common cause for RA in different patients. Rabbit anti-Id will also be used to screen serum IgG (of non-RA patients) known to contain high titers of antibodies agaist defined viral, bacterial, or food antigens to detect Id cross- reactivity. Such cross-reactivity with antibodies against any of these antigens would provide a potential link to the immune stimulus in RA. In a patient with Id cross-reactivity, rabbit anti-Id can be used to measure the reactive IgG in RA serum or synovial fluid to correlate its concentration with changes in disease activity and/or response to therapy. The upper 0.1 mm of RA cartilage contains IgG, IgM, and C3 in insoluble form, compatible with IC. Similar IC are found in the vacuoles of polymorphonuclear leukocytes in synovial fluid. IC will be isolated from both sources to detect non-Ig and non-complement antigens capable of stimulating the adjacent synovium. Cartilage will also be stained using F(ab)'2 fragments (not reactive with rheumatoid factors) of fluorescein or peroxidase-labeled rabbit anti-Id to link the trapped IgG to that being produced in the adjacent synovium.